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目的 :观察人体对抗癌新药尿多酸肽注射液的耐受性、毒性反应及与剂量的关系 ,确定人体安全耐受剂量。方法 :采用改良的Fibonacci方法 ,从低剂量逐渐上升至高剂量 ,每剂量组至少 3例受试者 ,初始剂量为尿多酸肽注射液 10 0mL·d- 1 ,iv ,连用 5d ,如无明显毒性反应则进入下一剂量组 ,直至达到最大耐受量 (MTD)。根据爬坡结果推荐Ⅱ期临床用药剂量 ,再选 3例患者按其剂量 ,连用 4周 ,进行疗程耐受性试验。结果 :2 0例肿瘤患者进入试验 ,分别进行了 5个剂量组的研究。主要毒性反应为静脉炎 ,其次是轻度的胃肠道反应 ,MTD为 5 0 0mL·d- 1 。3例接受疗程耐受性试验患者 ,采用锁骨下静脉置管给药 ,无静脉炎出现 ,未观察到明显毒性反应。结论 :尿多酸肽注射液毒性反应轻 ,患者耐受性好。推荐Ⅱ期临床使用剂量及方法为 :30 0mL·d- 1 ,深静脉给药 ,连用 4周。
OBJECTIVE: To observe the tolerance, toxicity and dose relationship of the new anti-cancer drug uroxacid injection and to determine the safe dose of human body. Methods: The improved Fibonacci method was used to gradually increase from low dose to high dose. At least 3 subjects in each dose group were given initial doses of 100 mL · d-1 of uroacitide injection for 5 days, Toxicity then entered the next dose group until the maximum tolerated dose (MTD) was reached. According to the results of climbing recommended phase Ⅱ clinical dose, and then select the three patients according to their dose, once every 4 weeks, the course of tolerance test. Results: Tumor patients were included in the study, and five dose groups were studied. The main toxic reaction was phlebitis, followed by a mild gastrointestinal reaction with a MTD of 500 mL · d -1. Three patients who underwent the course of tolerance test were treated with subclavian vein catheterization without phlebitis and no obvious toxicity was observed. Conclusion: Urease peptide injection has mild toxicity and good patient tolerance. The recommended dosage and method of phase Ⅱ clinical trial was 30 0 mL · d-1, administered in deep vein for 4 weeks.